Courses Of Cisplatin-based Chemotherapy Research Articles

The Role of Adjuvant Treatment in Low-Stage Germ Cell TesticularTumors

To find out up-to-date indications to adjuvant therapy in low-stage germ cell tumors (GCT) of the testis. The authors reviewed the material of the National Cancer Institute in Milan and the major international papers on adjuvant therapies of GCT of the testis. Moderate dose irradiation of retroperitoneal nodes remains the standard therapy of stage I seminoma; mediastinal irradiation has been abandoned in stage II seminoma. Nerve-sparing retroperitoneal lymph node dissection and surveillance remain standard therapies for nonseminomatous stage I tumors; 2 adjuvant courses of cisplatin-based chemotherapy are under investigation in high-risk patients. Postoperative adjuvant chemotherapy is mandatory only in bulky pathological stage II non-seminoma, but it is advisable also in patients who cannot be carefully followed. The cure rates of GCT of the testis can approach 100% in low stages and similar results can be achieved with different treatment modalities, but the maximum results can be obtained in specialized centers only.

Extragonadal Germ Cell Tumor of Retroperitoneal Origin: Report of Two Cases

Two cases of primary extragonadal germ cell tumor of retroperitoneal origin are reported. One was a 26-year-old man complaining of back pain. He had a large retroperitoneal tumor with lung, liver and supraclavicular lymph node metastases. He was referred to us after being treated for malignant lymphoma. The serum AFP, beta-subunit of human chorionic gonadotropin (hCG-beta), CEA and CA-19-9 were elevated. The retroperitoneal disease was treated surgically and with radiotherapy. The pathological diagnosis was that of embryonal carcinoma and teratoma. The lung, liver and supraclavicular lymph node metastases disappeared completely after two courses of cisplatin-based chemotherapy. While further chemotherapy was postponed due to myelosuppression, the disease relapsed and was resistant to subsequent therapy. The patient died twelve months after he first saw us. The second case was that of a 36-year-old man complaining of edematous legs and external genitalia. He had an extensive retroperitoneal tumor with multiple pulmonary metastases. The serum AFP level was high. Suspected of having an extragonadal germ cell tumor, he was referred to us promptly. Cisplatin-based chemotherapy coupled with resection of residual retroperitoneal and pulmonary disease resulted in complete remission. The pathological diagnosis was that of possible embryonal carcinoma. Further chemotherapy was given as scheduled, using granulocyte colony-stimulating factor. The patient has been in complete remission for two years. The chemotherapeutic regimen and surgical policy in the treatment of the two patients were essentially same. Early diagnosis, adequate initial therapy and the use of granulocyte colony-stimulating factor may be relevant to the favorable prognosis in the latter case.

Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer

The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI ⩽ 1.8% ( P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers ( P = 0.001), more undifferentiated tumours ( P = 0.02) and postsurgical residual disease greater than 2 cm ( P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery ( P = 0.000).

Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections.

We review the long-term outcome of patients with viable nonteratomatous germ cell tumor (NTGCT) in retroperitoneal lymph node dissection (RPLND) specimens after primary or salvage chemotherapy, and the impact of postoperative therapy with two courses of standard-dose cisplatin-based induction chemotherapy. All patients with viable NTGCT in postchemotherapy RPLND specimens from surgeries performed at Indiana University between July 1975 and March 1991 were retrospectively reviewed. Of 580 postchemotherapy RPLNDs performed, 133 had viable NTGCT in their pathology specimens. Of these 580 postchemotherapy RPLNDs, 417 were performed after primary chemotherapy, and 43 (10%) had viable NTGCT in their pathology specimens. There were 163 RPLNDs performed after salvage chemotherapy and 90 (55%) had viable NTGCT in their pathology specimens. After primary chemotherapy, 34 of 43 had complete resections, and 27 of the 34 received postoperative cisplatin-based chemotherapy. Nineteen of 27 (70%) are continuously disease-free (c-NED). All seven who received no postoperative chemotherapy have relapsed. After salvage chemotherapy, 53 of 90 had complete resections. Of those 53, 25 received postoperative chemotherapy, and nine (36%) are c-NED. Twenty-eight received no postoperative chemotherapy, and 12 (43%) are c-NED. Overall, 43 of 133 patients had incomplete resections, and only four are currently disease-free. There were four postoperative deaths (PODs). (1) Incomplete resection of viable NTGCT after primary or salvage chemotherapy portends a very poor prognosis. (2) For patients with complete resection of viable NTGCT following primary chemotherapy, two additional courses of cisplatin-based chemotherapy appear to be safe and effective therapy for reducing the risk of relapse. (3) Additional standard-dose chemotherapy appears to offer no benefit to patients with viable NTGCT in the resected specimen after salvage chemotherapy.

Outcome of patients with unfavorable optimally cytoreduced ovarian cancer treated with chemotherapy and whole abdominal radiation

There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despite optimal cytoreduction of tumor and abdominopelvic radiation. This study examined whether the survival of these patients, who have tumor with unfavorable histopathological characteristics and/or small residual disease, could be improved by giving chemotherapy before radiation. Forty-four out of fifty-one eligible patients, seen between 1981 and 1985, with Stage II or III disease were entered into the study. Following six courses of cisplatin-based chemotherapy, 33 (75%) received abdominopelvic radiotherapy. Survival was compared to that of 48 eligible matched control patients, treated with radiation between 1978 and 1981. The median follow-up is 6.6 years. The median survival was extended from 2.4 to 5.7 years ( P = 0.13), and 42.6% of patients receiving combined therapy were free of relapse at 5 years, compared to 21.6% ( P = 0.03) in the historical control group, treated with abdominopelvic irradiation alone. Only 2 of 44 patients in the combined group required surgery for bowel obstruction, as did 1 of 48 in the control group. Tolerance and toxicity of the combined approach were acceptable. Although we cannot be certain that the entire benefit we observed was not attributable to the chemotherapy alone, there is evidence that the radiotherapy may have been additive. Chemotherapy followed by abdominopelvic radiotherapy seems a reasonable management policy in these patients.

Second-look laparotomy in ovarian carcinoma patients after 8 and after 12 courses of cisplatin-based chemotherapy.

Sixteen ovarian carcinoma patients who received 12 courses and 21 patients who received 8 courses of cisplatin-based combination chemotherapy were compared. The two groups showed similar rates of second-look laparotomy (10/16 vs. 14/21) and similar rates of negative second-look laparotomies (6/10 vs. 9/14). The advantages of earlier reexploration are possibly lower toxicity and earlier recognition of patients with tumors resistant to the initial chemotherapy.

The measurement of cisplatin-DNA adduct levels in testicular cancer patients

Seventeen patients with 'poor prognosis' non-seminomatous testicular cancer were monitored for formation of intrastrand bidentate N7-d(ApG)- and N7-d(GpG)-diammineplatinum adducts in peripheral blood cell DNA during the course of cisplatin-based chemotherapy. Adduct values from blood cell DNA samples were compared with disease response data from the same individuals. Patients who received a dose of 40 mg/m2 cisplatin for 5 days generally formed more adducts than patients receiving 20 mg/m2 for 5 days, and adduct levels ranged from 0 to approximately 300 amol/micrograms DNA. Among the individuals who achieved a complete response, the median adduct level was 170 amol/micrograms DNA and the mean was 162. Among the individuals who achieved a partial response, the median adduct level was 78 amol/micrograms DNA and the mean was 83. Comparison of adduct levels between response groups using the Mann-Whitney test gave a two-sided P value of 0.072 (one-sided P value 0.036). Of 11 patients forming high levels of adduct (greater than 140 amol/micrograms DNA), 10 achieved a complete response; this compares with two complete responders in the group of six patients forming low levels (less than 100 amol/micrograms DNA) of adduct (P = 0.055, two-sided Fisher exact test). We conclude that cisplatin-DNA adduct formation in peripheral blood cell DNA correlates with the occurrence of complete response in patients with poor prognosis testicular cancer.